WNK2 p.Ala2139=
c.6417C>T · VCV3816500
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00336%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.051 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.2 | GERP -3.7 |
| Overall | ||
| CADD | 4.713 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00336%
Admixed American · 2/59,492 alleles
Filtering AF
0.000689%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.00112%
18/1,608,768 alleles · very rare
exomes 17/1,456,586 · genomes 1/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00336% | 29,746 |
| African / African-American | 0.00267% | 37,419 |
| European (non-Finnish) | 0.00119% | 84,162 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- WNK2
- Protein
- p.Ala2139=
- Coding
- c.6417C>T
- MANE Select
- NM_006648
- Type
- single nucleotide variant
- Location
- chr9:93308485 (GRCh38)
- Gene constraint
- LOEUF 0.508 · pLI 0.12 (gnomAD)
- Structure
- AlphaFold pLDDT 44.29 · 2 PDB
- Residue 2139
- the 'disordered' region
Similar variants
- WNK2 p.Ala2139Asp Uncertain significance ★ ⚠ same residue
- WNK2 p.Ala2139Thr Uncertain significance ★ ⚠ same residue
- WNK2 p.Pro1819Leu Uncertain significance ★★ ⚠ same type
- WNK2 c.2190+7G>A Benign ★★ same type
- WNK2 p.Ala2109= Benign/Likely benign ★★ same type
- WNK2 p.Ala808= Likely benign ★★ same type
- WNK2 p.Arg1849Trp Likely benign ★★ same type
- WNK2 p.Gly908Ala Benign ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/wnk2-p-ala2139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown